Human aggression constitutes a complex a multidetermined act which results in physical or verbal assault to others, self, or objects. Research into the etiologic determinants of premeditated and impulsive human aggression have focused on various sociologic, psychologic, and biogenetic factors. Among these, the most consistent biogenetic factor associated with impulsive (but not premeditated) aggression is a reduction in the activity of the central monoamine neurotransmitter serotonin (5-HT). 5-HT's role in the regulation of impulsive aggressive behavior is thought to arise from its role in neuronal inhibition, through which it raises the threshold for action in response to an outward (or inward) stimulus. In this formulation, 5-HT acts to restrain the individual from assaulting the object of stimulus. Empirically, a role for central 5-HT in the regulation of impulsive aggression and/or suicidal (i.e., of a violent and/or impulsive nature) behavior in humans is suggested by the association of reductions in indices of pre-synaptic activity (e.g. brain 5-HT/5-HIAA; lumbar CSF 5-HIAA; brain 3-H-IMI binding; platelet 3-H-IMI binding; platelet 5-HT uptake) in psychiatric patients with prominent histories of impulsive aggressive and suicidal behavior. Experimental data from animal studies strongly suggest an inverse relationship between "overall" central 5-HT activity and aggression. Further, reduced PRL responses to the 5-HT releaser/uptake inhibitor FENFLURAMINE (i.e., reflected by peak PRL[FEN] values) in mood/personality disordered patients with history of attempted suicide and prominent histories of impulsive aggression suggest that reduced "overall" central 5-HT activity is also associated with these behaviors in humans. If central 5-HT plays an important role in the regulation of impulsive aggressive and suicidal behaviors, then treatment with a potent and selective 5-HT enhancing agent should diminish impulsive aggressive and/or suicidal behaviors in patients with prominent histories of these behaviors. Patients with primary personality disorder (PD) belong to a group for which impulsive aggressive and suicidal behaviors are particularly prominent. Moreover, central 5-HT function has been shown to correlate inversely with these behaviors in these patients. Hence, the present study proposes to test the primary hypothesis that a pharmacologic treatment which putatively enhances central 5-HT function (i.e., FLUOXETINE, a potent and selective inhibitor of central 5-HT uptake) will be more efficacious than placebo in the treatment of impulsive aggressive behavior in patients with DSM-III-R personality disorder. The study's second hypothesis is that there will be a relationship between a pre-treatment index of central 5-HT system function (i.e., PRL[FEN] values) and the "anti-aggressive" effect of FLUOXETINE in these patients. To our knowledge, this represents the first double-blind placebo-controlled trial to assess the efficacy of FLUOXETINE (and to do so with pre-treatment measures of central 5-HT system function) in the treatment of impulsive aggressive behavior as a behavioral dimension in DSM-III-R personality disorder patients.